Research Projects

The increasing interest in three-dimensionally shaped sp3-rich scaffolds within medicinal chemistry has significantly propelled advancements in synthetic chemistry, particularly in the synthesis of saturated bioisosteres of hetero(arenes). Drug candidates that incorporate these 3D frameworks often show improved solubility, lipophilicity, and metabolic stability compared to their planar counterparts. Although 3D bioisosteres of hetero(arenes) offer significant advantages, their synthesis remains limited and is highly sought after through environmentally friendly methods. Current strategies for synthesizing these compounds largely depend on ring-strain chemistry. However, the high reactivity of ring-strain molecules, such as bicyclo[1.1.0] butanes and [1.1.1]propellane, makes their synthesis challenging and tedious. Consequently, developing a sustainable and unified strategy to access a wide range of (hetero)bicycloalkanes is a highly appealing yet elusive goal. This proposal aims to establish innovative electrochemical cyclization strategies for the rapid synthesis of medicinally relevant (hetero)bicyclo[1.1.1]pentanes from tethered methylenecyclobutane substrates. Building on this foundation, we will extend our methodology to synthesize (hetero)bicyclo[2.1.1]hexanes and (hetero)bicyclo[3.1.1]heptanes by systematically varying the lengths of the tethers. To enhance the synthetic utility of these methods, we will also explore asymmetric variants to produce enantioenriched chiral (hetero)bicyclo[2.1.1]hexanes and (hetero)bicyclo[3.1.1]heptanes. Finally, we aim to gain mechanistic insights through cyclic voltammetry and ReactIR studies to improve our understanding of the underlying transformation pathways. The novel methodologies proposed will not only enable the formation of functionalized (hetero)bicycloalkanes but will also establish a strong foundation for developing new electrochemical-mediated strategies for synthesizing value-added chemicals. The simplicity and straightforward nature of our proposed research will have applications in both academia and industry.